National Institutes of Health • National Center for Complementary and Integrative Health

St. John’s Wort and Depression
:What the Science Says

October 2012

Scientific Evidence

Study results on the effectiveness of St. John’s wort for depression are not conclusive.

A 2009 systematic review of 29 international studies suggested that St. John’s wort may be better than a placebo and as effective as standard prescription antidepressants for major depression of mild to moderate severity. St. John’s wort also appeared to have fewer side effects than standard antidepressants. The studies conducted in German-speaking countries—where St. John’s wort has a long history of use by medical professionals—reported more positive results than those done in other countries, including the United States.

Two studies, both sponsored by NCCAM and the National Institute of Mental Health, did not have positive results. Neither St. John’s wort nor a standard antidepressant medication decreased symptoms of minor depression better than a placebo in a 2011 study. The herb was no more effective than placebo in treating major depression of moderate severity in a large 2002 study.

Basic research studies suggest that St. John’s wort may prevent nerve cells in the brain from reabsorbing certain chemical messengers, including dopamine and serotonin. These naturally occurring neurotransmitters are known to be involved in regulating mood, but much remains to be learned about exactly how they work.

Side Effects and Cautions

St. John’s wort interacts with other drugs and can cause serious side effects.

Combining St. John’s wort and certain antidepressants can lead to serotonin syndrome—a potentially life-threatening increase in serotonin levels. Symptoms range from tremor and diarrhea to very dangerous confusion, muscle stiffness, drop in body temperature, and even death.

Psychosis is a rare but possible side effect of taking St. John’s wort, particularly in people who have or are at risk for mental health disorders, including bipolar disorder.

Taking St. John’s wort can weaken many prescription medicines, such as:

Antidepressants

Birth control pills

Cyclosporine, which prevents the body from rejecting transplanted organs

Digoxin, a heart medication

Some HIV drugs including indinavir

Some cancer medications including irinotecan

Warfarin and similar medications used to thin the blood.

Other side effects of St. John’s wort are usually minor and uncommon and may include upset stomach and sensitivity to sunlight. Also, St. John’s wort is a stimulant and may worsen feelings of anxiety in some people.

Tips for Talking With Your Patients About St. John’s Wort

Most patients do not proactively disclose use of complementary health practices to their health care providers. Ask your patients about their use of complementary health practices, including herbs or other dietary supplements such as St. John’s wort. When you ask your patients, you can help ensure that they are fully informed and help them make wise health care decisions.

When talking with your patients, help them understand that:

They should not use St. John’s wort to replace conventional care or to postpone seeing a health care provider about a medical problem. If not adequately treated, depression can become severe.

Dietary supplements can act in the same way as drugs. Dietary supplements, in particular St. John’s wort, can cause medical problems if not used correctly or if used in large amounts, and some may interact with medications your patients take.

Many dietary supplements have not been tested in pregnant women, nursing mothers, or children. Little safety information on St. John’s wort for pregnant women or children is available, so it is especially important to talk with health experts if you are pregnant or nursing or are considering giving a dietary supplement to a child.

NCCIH Clinical Digest is a service of the National Center for Complementary and Integrative Health, NIH, DHHS. NCCIH Clinical Digest, a monthly e-newsletter, offers evidence-based information on complementary health approaches, including scientific literature searches, summaries of NCCIH-funded research, fact sheets for patients, and more.

The National Center for Complementary and Integrative Health is dedicated to exploring complementary health products and practices in the context of rigorous science, training complementary health researchers, and disseminating authoritative information to the public and professionals. For additional information, call NCCIH's Clearinghouse toll-free at 1-888-644-6226, or visit the NCCIH Web site at nccih.nih.gov. NCCIH is 1 of 27 institutes and centers at the National Institutes of Health, the Federal focal point for medical research in the United States.